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oai:docta.ucm.es:20.500.14352/1259632025-11-13T01:06:46Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Moyano-Cires Ivanoff, Paula Viviana author Flores, Andrea author Sanjuan, Javier author Plaza Hernández, José Carlos author Guerra Menéndez, Lucía author Abascal, Luisa author Mateo Sierra, Olga author Pino Sans, Javier Del author 2025 Butylparaben (BP), a widely used preservative, was implicated in cognitive impairment, though its neurotoxic mechanisms remain elusive. Basal forebrain cholinergic neurons (BFCN) are selectively lost in dementias, contributing to cognitive decline. To explore different mechanisms related with BFCN loss, we employed BF SN56 cholinergic wild-type or silenced cells for Tau, amyloid-beta precursor protein (βApp), acetylcholinesterase (AChE), or glycogen synthase kinase-3 beta (GSK3β) genes, exposing them to BP (0.1-80 µM) for 1 or 14 days alongside triiodothyronine (T3; 15 nM), N-acetylcysteine (NAC; 1 mM), or recombinant heat shock protein 70 (rHSP70; 30 µM). BP disrupted cholinergic transmission by AChE inhibition and provoked cell death through thyroid hormones (THs) pathway disruption, Aβ/p-Tau protein accumulation, AChE-S overexpression, and oxidative stress (OS). Aβ/p-Tau accumulation was correlated with HSP70 downregulation, OS exacerbation, and GSK3β hyperactivation (for p-Tau). BP-induced OS was mediated by reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (NRF2) pathway disruption. All observed effects were contingent upon TH signaling impairment. These findings uncover novel mechanistic links between BP exposure and BFCN neurodegeneration, providing a framework for therapeutic strategies Moyano, P., Flores, A., Sanjuan, J., Plaza, J. C., Guerra-Menéndez, L., Abascal, L., Mateo, O., & Del Pino, J. (2025). Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment. Biology, 14(10), 1380. https://doi.org/10.3390/biology14101380 10.3390/biology14101380 https://hdl.handle.net/20.500.14352/125963 2079-7737 https://doi.org/10.3390/biology14101380 41154783 https://www.mdpi.com/2079-7737/14/10/1380 https://pubmed.ncbi.nlm.nih.gov/41154783/ Cholinergic Transmission Dysregulation and Neurodegeneration Induced by Thyroid Signaling Disruption Following Butylparaben Single and Repeated Treatment